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      Association between cannabis use and methadone maintenance treatment outcomes: an investigation into sex differences

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          Abstract

          Background

          Cannabis will soon become legalized in Canada, and it is currently unclear how this will impact public health. Methadone maintenance treatment (MMT) is the most common pharmacological treatment for opioid use disorder (OUD), and despite its documented effectiveness, a large number of patients respond poorly and experience relapse to illicit opioids. Some studies implicate cannabis use as a risk factor for poor MMT response. Although it is well established that substance-use behaviors differ by sex, few of these studies have considered sex as a potential moderator. The current study aims to investigate sex differences in the association between cannabis use and illicit opioid use in a cohort of MMT patients.

          Methods

          This multicentre study recruited participants on MMT for OUD from Canadian Addiction Treatment Centre sites in Ontario, Canada. Sex differences in the association between any cannabis use and illicit opioid use were investigated using multivariable logistic regression. A secondary analysis was conducted to investigate the association with heaviness of cannabis use.

          Results

          The study included 414 men and 363 women with OUD receiving MMT. Cannabis use was significantly associated with illicit opioid use in women only (OR = 1.82, 95% CI 1.18, 2.82, p = 0.007). Heaviness of cannabis use was not associated with illicit opioid use in men or women.

          Conclusions

          This is the largest study to date examining the association between cannabis use and illicit opioid use. Cannabis use may be a sex-specific predictor of poor response to MMT, such that women are more likely to use illicit opioids if they also use cannabis during treatment. Women may show improved treatment outcomes if cannabis use is addressed during MMT.

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          Most cited references35

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          The Prescription Opioid and Heroin Crisis: A Public Health Approach to an Epidemic of Addiction

          Annual Review of Public Health, 36(1), 559-574
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            Pharmacokinetics and pharmacodynamics of cannabinoids.

            Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30-90 minutes, reach their maximum after 2-3 hours and last for about 4-12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.
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              Sex differences in cannabinoid pharmacology: a reflection of differences in the endocannabinoid system?

              Marijuana is the most widely used illicit drug in the U.S., and marijuana use by women is on the rise. Women have been found to be more susceptible to the development of cannabinoid abuse and dependence, have more severe withdrawal symptoms, and are more likely to relapse than men. The majority of research in humans suggests that women are more likely to be affected by cannabinoids than men, with reports of enhanced and decreased performance on various tasks. In rodents, females are more sensitive than males to effects of cannabinoids on tests of antinociception, motor activity, and reinforcing efficacy. Studies on effects of cannabinoid exposure during adolescence in both humans and rodents suggest that female adolescents are more likely than male adolescents to be deleteriously affected by cannabinoids. Sex differences in response to cannabinoids appear to be due to activational and perhaps organizational effects of gonadal hormones, with estradiol identified as the hormone that contributes most to the sexually dimorphic effects of cannabinoids in adults. Many, but not all sexually dimorphic effects of exogenous cannabinoids can be attributed to a sexually dimorphic endocannabinoid system in rodents, although the same has not yet been established firmly for humans. A greater understanding of the mechanisms underlying sexually dimorphic effects of cannabinoids will facilitate development of sex-specific approaches to treat marijuana dependence and to use cannabinoid-based medications therapeutically. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                zielinsl@mcmaster.ca
                bhattm25@mcmaster.ca
                sangern@mcmaster.ca
                counselling@carolynplater.ca
                worster@mcmaster.ca
                mvarenbut@canatc.ca
                jdaiter@canatc.ca
                pareg@mcmaster.ca
                david.marsh@nosm.ca
                dipika.desai@phri.ca
                jmackill@mcmaster.ca
                mst@mcmaster.ca
                smcdermi@stjosham.on.ca
                thabanl@mcmaster.ca
                905 522 1155 , samaanz@mcmaster.ca
                Journal
                Biol Sex Differ
                Biol Sex Differ
                Biology of Sex Differences
                BioMed Central (London )
                2042-6410
                30 March 2017
                30 March 2017
                2017
                : 8
                : 8
                Affiliations
                [1 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, MiNDS Neuroscience Graduate Program, , McMaster University, ; Hamilton, ON Canada
                [2 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Health Research Methodology Graduate Program, , McMaster University, ; Hamilton, ON Canada
                [3 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Medical Science Graduate Program, , McMaster University, ; Hamilton, ON Canada
                [4 ]Canadian Addiction Treatment Centres, Hamilton, ON Canada
                [5 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Medicine, , McMaster University, ; Hamilton, ON Canada
                [6 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Population Genomics Program, Chanchlani Research Centre, , McMaster University, ; Hamilton, ON Canada
                [7 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Clinical Epidemiology and Biostatistics, , McMaster University, ; Hamilton, ON Canada
                [8 ]ISNI 0000 0000 8658 0974, GRID grid.436533.4, , Northern Ontario School of Medicine, ; Sudbury, ON Canada
                [9 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Psychiatry and Behavioural Neurosciences, , McMaster University, ; Hamilton, ON Canada
                [10 ]ISNI 0000 0001 0742 7355, GRID grid.416721.7, , Peter Boris Centre for Addictions Research, St. Joseph’s Healthcare Hamilton, ; Hamilton, ON Canada
                [11 ]ISNI 0000 0001 0742 7355, GRID grid.416721.7, Women’s Health Concerns Clinic, , St. Joseph’s Healthcare Hamilton, ; Hamilton, ON Canada
                [12 ]ISNI 0000 0004 1936 8227, GRID grid.25073.33, Department of Obstetrics and Gynaecology, , McMaster University, ; Hamilton, ON Canada
                [13 ]ISNI 0000 0001 0742 7355, GRID grid.416721.7, Cleghorn Early Intervention Clinic, , St. Joseph’s Healthcare Hamilton, ; Hamilton, ON Canada
                [14 ]ISNI 0000 0001 0742 7355, GRID grid.416721.7, Biostatistics Unit, Research Institute at St Joes, , St. Joseph’s Healthcare Hamilton, ; Hamilton, ON Canada
                Article
                130
                10.1186/s13293-017-0130-1
                5372283
                28367308
                fd4495b1-a35b-4924-982c-2edbbb21b4c4
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 November 2016
                : 7 March 2017
                Funding
                Funded by: CIHR Drug Safety and Effectiveness Network
                Award ID: 126639
                Award Recipient :
                Funded by: Peter Boris Centre for Addictions Research
                Funded by: Chanchlani Research Centre
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Human biology
                cannabis,opioid,opioid use disorder,methadone maintenance treatment,sex differences
                Human biology
                cannabis, opioid, opioid use disorder, methadone maintenance treatment, sex differences

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